CAR-T cell therapy has seen considerable success in the treatment of hematologic malignancies. In 2017, two CAR T-cell therapies were approved by the FDA, one for children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced lymphomas. However, the potential effectiveness of CAR-T therapies against solid tumors is still somewhat unknown. This project aims to identify small molecules capable of enhancing the killing activity of CAR-T cells, with a particular focus on liver cancers expressing a newly identified promising CAR-T target. The project team has outlined a critical assay path, and begun creating and optimizing a reporter cell line to enable high-throughput screening in conjunction with CAR-T cell treatment to identify compounds with potential additivity/synergy.